Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s

Daugan, Marie V.; Revel, Margot; Russick, Jules; Dragon-Durey, Marie-Agnès; Gaboriaud, Christine; Robe-Rybkine, Tania; Poillerat, Victoria; Grünenwald, Anne; Lacroix, Guillaume; Bougoüin, Antoine; Meylan, Maxime; Verkarre, Virginie; Oudard, Stéphane; Méjean, Arnaud; Vano, Yann; Perkins, Géraldine; Validire, Pierre; Cathelineau, Xavier; Sánchez-Salas, Rafael; Damotte, Diane; Frémeaux‐Bacchi, Véronique; Cremer, Isabelle; Sautès-Fridman, Catheriné; Fridman, Wolf H.; Roumenina, Lubka T.

doi:10.1158/2326-6066.cir-20-0532

Cited by 51 publications

(44 citation statements)

References 58 publications

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“…C1QBP was found to be closely related to tumorigenesis or metastasis of various cancers ( Bai et al, 2019 ; Xie et al, 2019 ; Peerschke et al, 2020 ; Egusquiza-Alvarez et al, 2021 ; Xie et al, 2021 ). C1S was also observed to promote tumor growth and survival in renal cancer and cutaneous squamous cell carcinoma ( Riihila et al, 2020 ; Daugan et al, 2021 ). The two genes are both mainly involved in the complement CP and are protumoral.…”

Section: Discussionmentioning

confidence: 99%

A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients

Zhang

Lin

Zhou

et al. 2022

Front. Cell Dev. Biol.

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The prognoses of sarcomas are poor and the responses of them to systemic therapies are limited and controversial. Thus, there is an urgent need to stratify the risk factors and identify the patients who may benefit from systemic therapies. Here, we developed a reliable, complement-based gene signature to predict the prognosis of sarcoma patients. Survival-related complement genes were identified by univariate Cox analyses and were used to build a gene signature, which was further selected using the least absolute shrinkage and selection operator model, and determined using a stepwise Cox proportional hazards regression model. The whole sarcoma cohort of TCGA was randomly divided into a training set and a test set. The signature was constructed using the training set and validated subsequently in the test set, the whole TCGA sarcoma cohort, and another two independent cohorts from the TARGET and GEO databases, respectively. Furthermore, the prognostic value of the signature was also validated in an independent cohort from our center. This model effectively predicted prognoses across the training set, different validation cohorts, and different clinical subgroups. Next, immune cell infiltration analysis, GO and KEGG analysis, and gene set enrichment analysis were performed to explore possible underlying mechanisms of this signature. Moreover, this signature may predict the response to immunotherapy. Collectively, the current complement-related gene signature can predict overall survival and possible immunotherapy response of sarcoma patients; it may serve as a powerful prognostic tool to further optimize clinical treatment and prognosis management for sarcoma patients.

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Section: Discussionmentioning

confidence: 99%

A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients

Zhang

Lin

Zhou

et al. 2022

Front. Cell Dev. Biol.

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“…T-cells play an important role in the tumor topology and efficacy of various therapeutic strategies for ccRCC (36). In addition, ccRCC with high expression of C4-activating enzyme C1s, may involve the infiltration of macrophages and T cells (37). Therefore, whether the risk score of our prognosis model is associated with immune cell infiltration was explored.…”

Section: Discussionmentioning

confidence: 99%

A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

et al. 2021

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Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma and has poor prognosis in the locally advanced stage. Ferroptosis, a relatively new type of cell death, has gained significant attention in recent years. This study aimed to explore the prognostic value of ferroptosis-related genes (FRGs) in ccRCC. In this study, 50 differentially expressed FRGs between ccRCC and adjacent normal kidney tissues were identified, 26 of them correlated with overall survival (OS) (P <0.05). Eight optimal FRGs were selected by Lasso regression and multivariate Cox regression analysis, and used to construct a new prognostic risk signature to predict the prognosis of ccRCC patients. In addition, the signature passed the validation of prognostic survival analyses by a significant margin, and the risk score was identified as an independent prognostic marker via Cox regression analyses. Further studies indicated that the signature was significantly correlated with immune cell infiltration. Moreover, the levels of eight FRGs were examined in ccRCC. Collectively, the 8-FRG prognostic risk signature helps the clinicians predict the prognosis and OS of the patients, and standardize prognostic assessments.

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“…While complement is activated on most tumor cells and promotes cell death, it does not result in cell killing and even promotes tumor progression in some cancer types. This finding can be explained by the low intratumoral expression of the components of the terminal pathway 3 and the limited formation of a membrane attack complex due to expression of specific inhibitors at the tumor cell surface 5,9,25 . Thus, chronic inflammation mediated by C5a favors an immunosuppressive microenvironment and facilitates T cells exhaustion 3,4 (Figure 3 point 4).…”

Section: C1q In the Complement Systemmentioning

confidence: 99%

C1q+ macrophages: passengers or drivers of cancer progression

Revel

Sautès-Fridman²,

Fridman³

et al. 2022

Trends in Cancer

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Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s

Cited by 51 publications

References 58 publications

A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients

A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients

A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

C1q+ macrophages: passengers or drivers of cancer progression

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